dbSNP rs10483452: PPP2R3C:c.1173+659T>G (chr14-35087292-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017917.4(PPP2R3C):c.1173+659T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,256 control chromosomes in the GnomAD database, including 3,956 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 3956 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP2R3C
NM_017917.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.22

Publications

12 publications found

Variant links:

Genes affected

PPP2R3C (HGNC:17485): (protein phosphatase 2 regulatory subunit B''gamma) This gene encodes a regulatory subunit of the serine/threonine phosphatase, protein phosphatase 2. This protein is localized to both nuclear and cytoplasmic regions depending on cell cycle phase. Homozygous conditional knockout mice for this gene exhibit reduced numbers and impaired proliferation of immune system B cells. This protein may regulate the expression of the P-glycoprotein ATP-binding cassette transporter through its phosphatase activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PPP2R3C links:

ENSG00000279434 (HGNC:):

ENSG00000279434 links:

FAM177A1 (HGNC:19829): (family with sequence similarity 177 member A1) This gene encodes a member of a conserved protein family. Alternative splicing results in multiple transcript variants. This gene is thought to be associated with susceptibility to juvenile idiopathic arthritis. [provided by RefSeq, Apr 2017]

FAM177A1 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics, G2P

FAM177A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R3C	NM_017917.4 link	c.1173+659T>G		intron_variant	Intron 12 of 12	ENST00000261475.10	NP_060387.2	Q969Q6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R3C	ENST00000261475.10 link	c.1173+659T>G		intron_variant	Intron 12 of 12	1	NM_017917.4	ENSP00000261475.5		Q969Q6-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31615

AN:

152138

Hom.:

3960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.0698

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.241

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.234

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.208

AC:

31614

AN:

152256

Hom.:

3956

Cov.:

AF XY:

0.202

AC XY:

15074

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0815

AC:

3387

AN:

41570

American (AMR)

AF:

0.208

AC:

3185

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1035

AN:

3468

East Asian (EAS)

AF:

0.0697

AC:

362

AN:

5192

South Asian (SAS)

AF:

0.146

AC:

704

AN:

4828

European-Finnish (FIN)

AF:

0.241

AC:

2552

AN:

10594

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19518

AN:

68010

Other (OTH)

AF:

0.232

AC:

490

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1237

2474

3712

4949

6186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.257

Hom.:

2848

Bravo

AF:

0.202

Asia WGS

AF:

0.106

AC:

368

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.0

(source)

DANN

Benign

0.47

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over